This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The erythrocyte (red blood cell, or RBC) membrane, including a lipid bilayer and a protein skeleton composed mostly of actin and spectrin, is routinely subjected to large deformations as the cell circulates throughout the body and squeezes through capillaries. We investigate the mechanical properties of this composite membrane by using a multi-scale model which incorporates a state-of-the-art understanding of the 3D molecular architecture of the skeleton, the skeleton-bilayer connectivity, the ?uid-structure interaction, and the constitutive law of the spectrin with stress-induced unfolding.